ResumenEl síndrome de Phelan McDermid es producido por una pér-dida de material genético, en un cromosoma del par 22, a nivel de la banda q13.3. Se describieron cinco pacientes con deleción 22q13.3 para correlacionar genotipo-fenotipo y comunicar el primer caso descripto en gemelas siamesas. Se registraron antecedentes perinatales, psicomotores, conducta, lenguaje y presencia de dismorfias. Se realizó cariotipo e hibridación in situ fluorescente (FISH) para región crítica 22q13.3. Presentaron hipotonía, dismorfias menores, retraso madurativo y retraso o ausencia del lenguaje. Se confirmó deleción 22q13.3 en los cinco pacientes, encontrándose una deleción en dos casos y un anillo del cromosoma 22 en tres, siendo uno con línea pura, y las siamesas, con mosaicismo, con una línea celular normal. En pacientes con clínica sugestiva y fenotipo evocador de sín-drome velo-cardio-facial, se debe realizar cariotipo y FISH para región crítica 22q11.2 con sonda control 22q13.3, para detectar la deleción del Síndrome de Phelan McDermid. Palabras clave: síndrome de deleción 22q13.3, retraso del desarrollo, ausencia de lenguaje, hipotonía. summaRy Phelan McDermid Syndrome is caused by the loss of genetic material in a chromosome from pair 22, at the band q13.3. We describe five patients with deletion 22q13.3 in order to establish a genotype-phenotype association, and report the first case described in conjoined twins. We analyzed the perinatal history, psychomotor behavior, language, and the presence of minor dysmorphism. Karyotypes and in situ hibridization (FISH) for critical region 22q13.3 were performed to all patients. 1 es conocido también como deleción 22q13.3 o monosomía 22q13.3, y representa un trastorno causado por la pérdida de material genético en el extremo terminal del brazo largo de un cromosoma del par 22, a nivel de la banda 22q13.3.2,3 Esta pérdida puede deberse a una deleción, 2,4,5 una translocación desbalanceada, 2 o a la formación de un anillo del cromosoma 22. El 80% de las deleciones se producen de novo, 6 aunque un 10% resultan de una translocación parental y encierran un mayor riesgo de recurrencia. 2Esta entidad se caracteriza por hipotonía neonatal, retraso global del desarrollo, ausencia o grave retraso en la adquisición del lenguaje, autismo y dismorfias menores. 2,3,7 El diagnóstico se realiza mediante estudio citogenético, hibridación in situ fluorescente (FISH), hibridación genómica comparada (HGC), MLPA (multiplex ligation dependent probe amplification) o microarrays.Nuestro objetivo fue intentar correlacionar genotipo y fenotipo en cinco pacientes con deleción 22q13.3, agrupar las características distintivas y comunicar el primer caso diagnosticado, en gemelas siameses.

Background: To conduct the first large-scale genetic analysis of inherited eye diseases (IED) in Argentina and describe the comprehensive genetic profile of a large cohort of patients. Methods: This is a retrospective study analyzing medical records of 22 ophthalmology and genetics services throughout 13 Argentinian provinces. Patients with a clinical diagnosis of an ophthalmic genetic disease and a history of genetic testing were included. Medical, ophthalmological and family history was collected. Results: 773 patients from 637 families were included, with 98% having inherited retinal disease. The most common phenotype was retinitis pigmentosa (RP, 62%). Causative variants were detected in 377 (59%) patients. USH2A, RPGR, and ABCA4 were the most common disease-associated genes. USH2Awas the most frequent gene to cause RP, RDH12 early onset severe retinal dystrophy, ABCA4 Stargardt disease, PROM1 cone-rod dystrophy, and BEST1 macular dystrophy. The most frequent variants were RPGRc.1345C>T, p.(Arg449*) and USH2A c.15089C>A, p.(Ser5030*). The study revealed 159/448 (35%) previously unreported pathogenic/likely pathogenic variants and 5 likely founder mutations. Conclusions: We present the genetic landscape of IED in Argentina and the largest cohort in South America. This data will serve as a reference for future genetic studies, aid diagnosis, inform counselling, and assist in addressing the largely unmet need for clinical trials to be conducted in the region.

This study corresponds to the first large-scale genetic analysis of inherited eye diseases (IED) in Argentina and describes the comprehensive genetic profile of a large cohort of patients. Medical records of 22 ophthalmology and genetics services throughout 13 Argentinian provinces were analyzed retrospectively. Patients with a clinical diagnosis of an ophthalmic genetic disease and a history of genetic testing were included. Medical, ophthalmological and family history was collected. A total of 773 patients from 637 families were included, with 98% having inherited retinal disease. The most common phenotype was retinitis pigmentosa (RP, 62%). Causative variants were detected in 379 (59%) patients. USH2A, RPGR, and ABCA4 were the most common disease-associated genes. USH2A was the most frequent gene associated with RP, RDH12 early-onset severe retinal dystrophy, ABCA4 Stargardt disease, PROM1 cone-rod dystrophy, and BEST1 macular dystrophy. The most frequent variants were RPGR c.1345 C > T, p.(Arg449*) and USH2A c.15089 C > A, p.(Ser5030*). The study revealed 156/448 (35%) previously unreported pathogenic/likely pathogenic variants and 8 possible founder mutations. We present the genetic landscape of IED in Argentina and the largest cohort in South America. This data will serve as a reference for future genetic studies, aid diagnosis, inform counseling, and assist in addressing the largely unmet need for clinical trials to be conducted in the region.